The main objective of the research project is to elucidate the molecular mechanism of disorder in the ionic channels of myotonic muscles. Both the voltage clamp analysis and single channel recording techniques are being applied to examine the nature of ionic channels in muscles of experimental myotonia. The overall conductances of sodium, potassium, and chloride channels are assessed by their current-voltage relationship. The functional status of each type of channels are studied by the kinetic analysis of the voltage-dependent activation and inactivation parameters. The influence of temperature on channel conductances are also to be examined to determine the exact nature of the well known inverse temperature dependence of myotonia. The results of the temperature effect may be used to differentiate the abnormal ionic channels from the normal ones. The quantitative measurement of the heat of activation may help us to interpret the nature of lipid-protein interaction between the ionic channels and membrane lipids. The single channel recording technique is being applied to study the kinetic behavior of individual sodium channels. With the gigaseal patch clamp technique, currents flowing through each individual channel can be recorded. The data obtained from both the macroscopic and microscopic currents will be integrated to identify the fundamental mechanism underlying the disorders of human myotonia.